The normal motility patterns of the gastrointestinal tract are largely dependent on intrinsic nervous reflexes. Pathological changes in these enteric neurons underly many motility disorders. Our progress in understanding how movements of the gastrointestinal tract are controlled has been considerably hampered by our lack of understanding of the nerve circuits involved. The experiments outlined in this proposal are designed to address this deficiency. This study will determine the intrinsic neuronal circuitry underlying motility reflexes in the ileum, proximal colon and distal colon of the guinea pig. Intracellular recording techniques will be used to correlate reflex responses of enteric neurons to distension, mechanical brushing of the mucosa and chemical stimulation (Hcl) of the mucosa with responses in longitudinal and circular smooth muscle cells to similar stimuli. A novel preparation consisting of an opened segment of intestine pinned with the mucosa uppermost over 1 or 2 balloons has been designed to facilitate intracellular recordings from both enteric neurons and smooth muscle cells. This preparation allows any of the above stimuli to be applied separately or interacted at areas oral and anal and even circumferential to the recording site. Once the response of an impaled neuron to one or each of the stimuli has been determined it will be injected with a dye through the recording microelectrode. The projections of the neuron through the myenteric plexus or to either muscle layer will then be traced, and the neuron functionally identified as either a sensory, interneuron or motor neuron in a particular nervous reflex pathway or as a neuron common to several reflex pathways. In the intestine motility would be expected to result from the summation of reflexes activated by mechanical and chemical stimulation of the mucosal villi as well as by distension of the lumen. The contribution of the mucosa to distension reflexes, and interactions between reflex pathways initiated by the three stimuli will be investigated. By comparing the derived circuitry in these three functionally different regions of the gastrointestinal tract some crucial principles of enteric organizations will be determined.